Approach towards an integrative drug treatment of Alzheimer’s disease

  • M. Windisch
Conference paper


At present pharmacotherapy of Alzheimer’s disease (AD) is limited to acetylcholinesterase inhibitors. These drugs produce small, but consistent improvements of memory and global function, some are also positively influencing activities of daily living. This therapeutic approach neglects the complexity of AD and the fact that most of the degenerating neurons are not cholinergic. Acetylcholinesterase inhibitors are symptomatic drugs, with no influence on disease progression.

There is a need for disease modifying compounds, or preventive drugs. Data are indicating that vitamin E has some ability to influence the disease progression. The potency of non-steroidal anti-inflammatory drugs (NS AIDs) or estrogen as preventive agents has to be explored further in prospective clinical studies. The initial hope in the use of naturally occurring neurotrophic factors, like nerve growth factor, to rescue cholinergic neurons from degeneration and to restore cognitive function has been disappointed in first, small clinical studies. The peptidergic drug Cerebrolysin® exhibiting neurotrophic stimulation, neuroimmunotrophic regulation and induction of BBB glucose transporter expression, might be able to address the pathological changes of AD at different levels simultaneously. In addition to an impressive preclinical database, results from 3 placebo-controlled, double-blind studies demonstrate significant improvements of cognitive performance, global function and activities of daily living in AD patients. In all studies persisting improvements, up to 6 months after drug withdrawal, indicate a powerful disease modifying activity.


Nerve Growth Factor Cholinesterase Inhibitor Acetylcholinesterase Inhibitor Cholinergic Hypothesis Amyloid Precursor Protein Metabolism 
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  1. Aisen PS, Davis KL (1997) The search for disease-modifying treatment for Alzheimer’s disease. Neurology 48 (6): 35 – 41Google Scholar
  2. Akai F, Hiruma S, Sato T, Iwamoto N, Fujimoto M, Ioku M, Hashimoto S (1992) Neurotrophic factor-like effect of FPF1070 on septal cholinergic neurons after transections of fimbria-fornix in the rat brain. Histol Histopathol 7: 213 – 221PubMedGoogle Scholar
  3. Albeck DS, Hoffer BJ, Quissell D, Sanders LS, Zerbe G, Granholm ACE (1997) A noninvasive transport system for GDNF across the blood-brain barrier. Neuroreport 8: 2293 – 2298PubMedCrossRefGoogle Scholar
  4. Albrecht E, Hingel S, Crailsheim K, Windisch M (1993) The effects of Cerebrolysin on survival and sprouting of neurons from cerebral hemispheres and from the brainstem of chick embryos in vitro. Adv Biosci 87: 341 – 342Google Scholar
  5. Amberla K, Nordberg A, Viitanen M, Winblad B (1993) Long-term treatment with tacrine (THA) in Alzheimer’s disease-evaluation of neuropsychological data. Acta Neurol Scand 149: 55 – 57Google Scholar
  6. Anand R, Gharabawi G (1996) Clinical development of ExelonTM (ENA-713): The Adena programme. J Drug Devel Clin Practice 8: 117 – 122Google Scholar
  7. Anand R, Gharabawi G, Enz A (1996) Efficacy and safety results of the early phase studies with ExelonTM (ENA-713) in Alzheimer’s disease: an overview. J Drug Devel Clin Practice 8: 109 – 116Google Scholar
  8. Balson R, Gibson PR, Ames D, Bhathal PS (1995) Tacrine-induced hepatotoxicity. CNS Drugs 4: 168 – 181CrossRefGoogle Scholar
  9. Becker RE, Colliver JA, Markwell SJ, Moriearty PL, Unni LK, Vicari S (1996) Double- blind, placebo-controlled study of Metrifonate, an acetylcholinesterase inhibitor, for Alzheimer disease. Alzheimer Dis Assoc Disord 10: 124 – 131PubMedCrossRefGoogle Scholar
  10. Boado RJ (1995) Brain-derived peptides regulate the steady state levels and increase stability of the blood-brain barrier GLUT1 glucose transporter mRNA. Neurosci Lett 197: 179 – 182PubMedCrossRefGoogle Scholar
  11. Boado RJ (1996) Brain-derived peptides increase the expression of a blood-brain barrier GLUT1 glucose transporter reporter gene. Neurosci Lett 220: 53 – 56PubMedCrossRefGoogle Scholar
  12. Boado RJ, Wu D, Pardridge WM, Windisch M (1999) In vivo upregulation of the blood-brain barrier GLUT1 glucose transporter by brain-derived peptides. Neurosci Res 34: 217 – 224PubMedCrossRefGoogle Scholar
  13. Bores GM, Huger FP, Petko W, Mutlib AE, Camacho F, Rush DK, Selk DE, Wolf V (1996) Pharmacological evaluation of novel Alzheimer’s disease therapeutics: Acetylcholinesterase inhibitors related to galanthamine. J Pharmacol Exp Ther 277: 728 – 738PubMedGoogle Scholar
  14. Breitner JCS (1996) Inflammatory processes and antiinflammatory drugs in Alzheimer’s disease: a current appraisal. Neurobiol Aging 17: 789 – 794PubMedCrossRefGoogle Scholar
  15. Cordell B (1994) β-Amyloid formation as a potential therapeutic target for Alzheimer’s disease. Annu Rev Pharmacol Toxicol 34: 69–89Google Scholar
  16. Crook TH, Petrie W, Wells C, Massari D (1992) Effects of phosphatidylserine in Alzheimer’s disease. Psychopharmacol Bull 28: 61 – 66PubMedGoogle Scholar
  17. Cummings BJ, Pike ChJ, Shankle R, Cotman CW (1996) β-Amyloid deposition and other measures of neuropathology predict cognitive status in Alzheimer’s disease. Neurobiol Aging 17/6: 921–933Google Scholar
  18. Cummings J, Bieber F, Mas J, Orazem J, Gulanski B (1997) Metrifonate in Alzheimer’s disease: results of a dose-finding study. In: Iqbal K, Winblad B, Nishimura T, Takeda M, Wisniewski HM (eds) Alzheimer’s disease: biology, diagnosis and therapeutics. John Wiley, Chichester, pp 656-669 Cutler RN, Sramek J (1993) Tacrine in alzheimer’s disease. N Engl J Med 808. Davis LK, Thai JL, Gamzu ER, Davis SH, Woolson RF, Gracon ST, Drachman DA (1992) A double-blind placebo-controlled multicenter study of tacrine for Alzeheimer’s disease. N Engl J Med 327: 1253 – 1259Google Scholar
  19. Doody RS (1999) Clinical profile of donepezil in the treatment of Alzheimer’s disease. Gerontology 45 [Suppl 1]: 23 – 32PubMedCrossRefGoogle Scholar
  20. Ebert U, Kirch W (1998) Review — Scopolamine model of dementia: electroencephalogram findings and cognitive performance. Eur J Clin Invest 28: 944-949 Ferris SH, Mackell JA, Mohs R, Schneider LS, Galasko D, Whitehouse PJ, Schmitt FA, Sano M, Thomas RG, Ernesto C, Grundman M, Schafer K, Thai LJ (1997) A multicenter evaluation of new treatment efficacy instruments for Alzheimer’s disease clinical trials: Overview and general results. Alzheimer Dis Assoc Disord 11: S1 – S12Google Scholar
  21. Flood JF, Cherkin A (1986) Scopolamine effects on memory retention in mice: A model of dementia. Behav Neural Biol 45: 169 – 184PubMedCrossRefGoogle Scholar
  22. Francis PT, Palmer AM, Snape M, Wilcock GK (1999) The cholinergic hypothesis of Alzheimer’s disease: a review of progress. J Neurol Neurosurg Psychiatry 66: 137– 147Google Scholar
  23. Francis-Turner L, Valouskova V (1996) Nerve growth factor and nootropic drug Cerebrolysin but not fibroblast growth factor can reduce spatial memory impairment elicited by fimbria-fornix transection: short-term study. Neurosci Lett 202: 1 – 4CrossRefGoogle Scholar
  24. Fratiglioni L, DeRonchi D, AgueroTorres H (1999) Worldwide prevalence and incidence of dementia. Drugs Aging 15: 365 – 375PubMedCrossRefGoogle Scholar
  25. Freeman SE, Dawson RM (1991) Tacrine: A pharmacological review. Prog Neurobiol 36: 257 – 277PubMedCrossRefGoogle Scholar
  26. Growdon JH, Corkin S, Huff FJ, Rosen TJ (1986) Piracetam combinded with lecithin in the treatment of Alzheimer’s disease. Neurobiol Aging 7: 269 – 276PubMedCrossRefGoogle Scholar
  27. Gschanes A, Windisch M (1998) The influence of Cerebrolysin and E021 on spatial navigation of 24-month-old rats. J Neural Transm [Suppl 53]: 313 – 321Google Scholar
  28. Gschanes A, Windisch M (1998) The influence of Cerebrolysin and E021 on spatial navigation of 24-month-old rats. J Neural Transm [Suppl 53]: 313 – 321Google Scholar
  29. Hardy J (1997) Amyloid, the presenilins and Alzheimer’s disease. TINS 20: 154 – 159PubMedGoogle Scholar
  30. Hefti F (1999) Nerve growth factor treatment for Alzheimer’s disease: The experience of the first attempt at intracerebral neurotrophic factor therapy. In: Hefti F (ed), Neurotrophic factors, Springer Berlin Heidelberg New York Tokyo, pp 175 – 187Google Scholar
  31. Hefti F, Schneider LS (1991) Nerve growth factor and Alzheimer’s disease. Clin Neuropharmacol 14 /1: 62 – 76Google Scholar
  32. Hellweg R, von Richthofen S, Anders D, Baethge C, Ropke S, Hartung HD, Gericke CA (1998) The time course of nerve growth factor content in different neuropsychiatric diseases — a unifying hypothesis — Review article. J Neural Transm 105: 871 – 903PubMedCrossRefGoogle Scholar
  33. Henderson,VW (1997a) Estrogen replacement therapy for the prevention and treatment of Alzheimer’s disease. CNS Drugs 8: 343 – 351CrossRefGoogle Scholar
  34. Henderson VW (1997b) The epidemiology of estrogen replacement therapy and Alzheimer’s disease. Neurology 48: 27 – 35Google Scholar
  35. Hock C, Heese K, Muller-Spahn F, Hulette C, Rosenberg C, Otten U (1998) Decreased trkA neurotrophin receptor expression in the parietal cortex of patients with Alzheimer’s disease. Neurosci Lett 241: 151 – 154PubMedCrossRefGoogle Scholar
  36. Holford NHG, Peace K (1994) The effect of tacrine and lecithin in Alzheimer’s disease. A population pharmacodynamic analysis of five clinical trials. Eur J Clin Pharmacol 47: 17 – 23PubMedGoogle Scholar
  37. Hull M, Fiebich BL, Schumann G, Lieb K, Bauer J (1999) Anti-inflammatory substances a new therapeutic option in Alzheimer’s disease. Drug Discov Today 4: 275 – 282PubMedCrossRefGoogle Scholar
  38. Hutter-Paier B, Grygar E, Windisch M (1996) Death of cultured telencephalon neurons induced by glutamate is reduced by the peptide derivative Cerebrolysin. J Neural Transm 47: 267 – 273Google Scholar
  39. Jette N, Cole MS, Fahnestock M (1994) NGF mRNA is not decreased in frontal cortex from Alzheimer’s disease patients. Mol Brain Res 25: 242 – 250PubMedCrossRefGoogle Scholar
  40. Jonhagen ME, Nordberg A, Amberla K, Backman L, Ebendal T, Meyerson B, Olson L, Seiger A, Shigeta M, Theodorsson E, Viitanen M, Winblad B, Wahlund LO (1998) Intracerebroventricular infusion of nerve growth factor in three patients with Alzheimer’s disease. Dement Geriatr Cogn Disord 9: 246 – 257CrossRefGoogle Scholar
  41. Kawas C, Resnick S, Morrison A, Brookmeyer R, Corrada M, Zonderman A, Bacal C, Lingle DD, Metter E (1997) A prospective study of estrogen replacement therapy and the risk of developing Alzheimer’s disease: The Baltimore Longitudinal Study of Aging. Neurology 48: 1517 – 1521PubMedGoogle Scholar
  42. Kisilevsky R (1996) Anti-amyloid drugs. Potential in the treatment of diseases associated with aging. Drugs Aging 8 /2: 75 – 83PubMedCrossRefGoogle Scholar
  43. Kittner B, Rössner M, Rother M (1997) Clinical trials in dementia with propentofylline. Ann N Y Acad Sci 826: 307 – 316PubMedCrossRefGoogle Scholar
  44. Knapp JM, Gracon StI, Davis SCh, Solomon PR, Pendlebury W, Knopman DS (1994) Efficacy and safety of high-dose tacrine: A 30-week evaluation. Alzheimer Dis Assoc Disord 8 /2: 22 – 31Google Scholar
  45. Koopmans Summers W, Majovski LV, Marsh GM, Tachiki K, Kling A (1986) Oral tetrahydroaminoacridine in long-term treatment of senile dementia, Alzheimer type. N Engl J Med 315: 1241 – 1245PubMedCrossRefGoogle Scholar
  46. Lansbury PT (1997) Inhibition of amyloid formation: a strategy to delay the onset of Alzheimer’s disease, chemical biology 1: 260 – 267Google Scholar
  47. Lindsay RM (1996) Therapeutic potential of the neurotrophins and neurotrophin-CNTF combinations in peripheral neuropathies and motor neuron diseases. Ciba Found Symp 196: 39 – 53PubMedGoogle Scholar
  48. Lombardi VRM, Windisch M, Garcia M, Cacabelos R (1999) Effects of Cerebrolysin on in vitro primary microglial and astrocyte rat cell cultures. Methods Find Exp Clin Pharmacol 21: 331 – 338PubMedCrossRefGoogle Scholar
  49. MacKenzie IRA (1996) Antiinflammatory drugs in the treatment of Alzheimer’s disease. J Rheumatol 23 /5: 806 – 808PubMedGoogle Scholar
  50. Masliah E, Armasolo F, Veinbergs I, Mallory M, Samuel W (1999) Cerebrolysin ameliorates performance deficits, and neuronal damage in apolipoprotein E-deficient mice. Pharmacol Biochem Behav 62: 239 – 245PubMedCrossRefGoogle Scholar
  51. Meier-Ruge W, Kolbe M, Sattler J (1991) Investigations of the cholinergic deficit hypothesis in the hippocampus of the aged rat brain with physostigmine and scopolamine. Arch Gerontol Geriatr 12: 239 – 251PubMedCrossRefGoogle Scholar
  52. Mor G, Nilsen J, Horvath T, Bechmann I, Brown S, GarciaSegura LM, Naftolin F (1999) Estrogen and microglia: A regulatory system that affects the brain. J Neurobiol 40: 484 – 496PubMedCrossRefGoogle Scholar
  53. Mufson EJ, Sobreviela T (1995) The NGF superfamily of neurotrophins: Potential treatment for Alzheimer’s and Parkinson’s disease. Behav Brain Sci 18: 63 – 65CrossRefGoogle Scholar
  54. Narisawa-Saito M, Wakabayashi K, Tsuji S, Takahashi H, Nawa H (1996) Regional specificity of alterations in NGF, BDNF and NT-3 levels in Alzheimer’s disease. Neuroreport 7: 1 – 4CrossRefGoogle Scholar
  55. Nitsch RM, Slack BE, Wurtman RJ, Growdon JH (1992) Release of Alzheimer amyloid precursor derivates stimulated by activation of muscarinic acetylcholine receptors. Science 258: 304 – 307PubMedCrossRefGoogle Scholar
  56. Nordberg A (1992) Biological markers and the cholinergic hypothesis in Alzheimer’s disease. Acta Neurol Scand 139: 54 – 58CrossRefGoogle Scholar
  57. Pan WH, Banks WA, Kastin AJ (1998) Permeability of the blood-brain barrier to neurotrophins. Brain Res 788: 87 – 94PubMedCrossRefGoogle Scholar
  58. Pan YL, Anthony M, Clarkson TB (1999) Evidence for up-regulation of brain-derived neurotrophic factor mRNA by soy phytoestrogens in the frontal cortex of retired breeder female rats. Neurosci Lett 261: 17 – 20PubMedCrossRefGoogle Scholar
  59. Pepeu G, Pepeu IM, Amaducci L (1996) A Review of Phoshatidylserine pharmacological and clinical effects. Is Phosphatidylserine a drug for the ageing brain? Pharmacol Res 33 /2: 73 – 80PubMedCrossRefGoogle Scholar
  60. Pollard BH, Rojas E, Arispe N (1994) β-Amyloid in Alzheimer’s disease. Therapeutic implications. CNS Drugs 2/1: 1–6Google Scholar
  61. Prentice N, Van Beck M, Dougall NJ, Moffoot PRA, O’Carroll RE, Goodwin GM, Ebmeier K (1996) A double-blind, placebo-controlled study of tacrine in patients with Alzheimer’s disease using SPET. J Psychopharmacol 10 /3: 175 – 181CrossRefGoogle Scholar
  62. Raffaele KC, Berardi A, Asthana S, Morris P, Haxby JV, Soncrant TT (1991) Effects of Long-therm continuous infusion of the muscarinic cholinergic agonist arecoline on verbal memory in dementia of the Alzheimer type. Psychopharmacol Bull 27β): 315– 319Google Scholar
  63. Robbins TW, McAlonan G, Muir JL, Everitt BJ (1997) Cognitive enhancers in theory and practice: studies of the cholinergic hypothesis of cognitive deficits in Alzheimer’s disease. Behav Brain Res 83: 15 – 23PubMedCrossRefGoogle Scholar
  64. Rogers SL, Friedhoff LT (1996) The efficacy and safety of Donepezil in patients with Alzheimer’s disease: Results of a US multicentre, randomized, double-blind, placebo-controlled trial. Dementia 7: 293 – 303PubMedGoogle Scholar
  65. Rogers SL, Friedhoff LT (1998) Long-term efficacy and safety of donepezil in the treatment of Alzheimer’s disease: an interim analysis of the results of a US multicentre open label extension study. Eur Neuropsychopharmacol 8: 67 – 75PubMedCrossRefGoogle Scholar
  66. Rogers SL, Farlow MR, Doody RS, Mohs R, Friedhoff LT, Albala B, Baumel B, Booker G, Dexter J, Farmer M, Feighne JP, Ferris S, Gordon B, Gorman DG, Hanna G, Harrell LE, Hubbard R, Kennedy J, McCarthy J, Scharre DW, Schaerf F (1998) A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer’s disease. Neurology 50: 136 – 145PubMedGoogle Scholar
  67. Roßner S, Ueberham U, Schliebs R, Perez-Polo JR, Bigl V (1998) The regulation of amyloid precursor protein metabolism by cholinergic mechanisms and neurotrophin receptor signaling. Prog Neurobiol 56: 541 – 569PubMedCrossRefGoogle Scholar
  68. Rother M, Erkinjuntti T, Roessner M, Kittner B, Marcusson J, Karlsson I (1998) Propentofylline in the treatment of Alzheimer’s disease and vascular dementia: A review of phase III trials. Dement Geriatr Cogn Disord 9 [Suppl 1]: 36 – 43PubMedCrossRefGoogle Scholar
  69. Rüther E, Ritter R, Apecechea M, Freytag S, Windisch M (1994) Efficacy of the peptidergic nootropic drug Cerebrolysin in patients with senile dementia of the Alzheimer type (SDAT). Pharmacopsychiatry 27: 32 – 40PubMedCrossRefGoogle Scholar
  70. Saitoh T, Brugge K (1994) Is amyloid causally involved in pathophysiology of Alzheimer’s disease? Neurobiol Aging 15 /4: 461 – 462PubMedCrossRefGoogle Scholar
  71. Sano M, Ernesto Ch, Klauber MR, Schafer K, Woodbury P, Thomas R, Grundman M (1996) Rationale and design of a multicenter study of selegiline and alpha-tocopherol in the treatment of Alzheimer disease using novel clinical outcomes. Alzheimer Dis Assoc Disord 10: 132 – 140PubMedCrossRefGoogle Scholar
  72. Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M, Woodbury P, Growdon J, Cotman CW, Pfeiffer E, Schneider LS, Thai LJ (1997) A controlled trial of Selegiline, Alpha-Tocopherol, or both as treatment for Alzheimer’s disease. N Engl J Med 336: 1216 – 1222PubMedCrossRefGoogle Scholar
  73. Satou T, Imano M, Akai F, Hashimoto S, Itoh T, Fujimoto M (1993) Morphological observation of effects of Cerebrolysin on cultured neural cells. Adv Biosci 87: 195 – 196Google Scholar
  74. Satou T, Itoh T, Fujimoto M, Hashimoto S (1994) Neurotrophic-like effects of FPF-1070 on cultured neurons from chick embryonic dorsal root ganglia. Jpn Pharmacol Ther 22 /4: 205 – 212Google Scholar
  75. Schwarz RD, Callahan MJ, Davis RE, Jaen JC, Tecle H (1997) Development of M-l subtype selective muscarinic agonists for Alzheimer’s disease: Translation of in vitro selectivity into in vivo efficacy. Drug Dev Res 40: 133 – 143CrossRefGoogle Scholar
  76. Seiger A, Nordberg A, von Hoist H, Backman L, Ebendal T, Alafuzoff I, Amberla K, Hartvig P, Herlitz A, Lilja A, Lundqvist H, Langstrom B, Meyerson B, Persson A, Viitanen M, Winblad B, Olson L (1993) Intracranial infusion of purified nerve growth factor to an Alzheimer patient: the first attempt of a possible future treatment strategy. Behav Brain Res 57: 255 – 261PubMedCrossRefGoogle Scholar
  77. Shumaker SA, Reboussin BA, Espeland MA, Rapp SR, McBee WL, Dailey M, Bowen D, Terrell T, Jones BN (1998) The Women’s Health Initiative Memory Study (WHIMS): A trial of the effect of estrogen therapy in preventing and slowing the progression of dementia. Control Clin Trials 19: 604 – 621PubMedCrossRefGoogle Scholar
  78. Si Q, Nakamura Y, Schubert P, Rudolphi K, Kataoka K (1996) Adenosine and propentofylline inhibit the proliferation of cultured microglial cells. Exp Neurol 137: 345 – 349PubMedCrossRefGoogle Scholar
  79. Singer CA, McMillan PJ, Dobie D J, Dorsa DM (1998) Effects of estrogen replacement on choline acetyltransferase and trkA mRNA expression in the basal forebrain of aged rats. Brain Res 789: 343 – 346PubMedCrossRefGoogle Scholar
  80. Soto C (1999) Beta-amyloid disrupting drugs — potential in the treatment of Alzheimer’s disease. CNS Drugs 12: 347 – 356CrossRefGoogle Scholar
  81. Stewart WF, Kawas C, Corrada M, Metter EJ (1997) Risk of Alzheimer’s disease and duration of NSAID use. J Neurol 48: 626 – 632Google Scholar
  82. Svensson AL, Nordberg A (1998) Tacrine and donepezil attenuate the neurotoxic effect of A beta(25–35) in rat PC12 cells. Neuroreport 9: 1519 – 1522PubMedCrossRefGoogle Scholar
  83. Tanzi ER, Vaula G, Romano DM, Mortilla M, Huang LT, Tupler GR, Wasco W, Hyman BT (1992) Assessment of amyloid β-protein precursor gene mutations in a large set of familial and sporadic Alzheimer disease cases. Am J Hum Genet 51: 273 – 282PubMedGoogle Scholar
  84. Terry RD (1996) The pathogenesis of Alzheimer disease: an alternative to the amyloid hypothesis. J Neuropathol Exp Neurol 55 /10: 1023 – 1025PubMedGoogle Scholar
  85. Thomsen T, Bickel U, Fischer JP, Kewitz H (1990) Galanthamine hydrobromide in a long-term treatment of Alzheimer’s disease. Dementia 1\ 46 – 51Google Scholar
  86. Valouskova V, Francis-Turner L (1998) Can Cerebrolysin influence chronic deterioration of spatial learning and memory? J Neural Transm [Suppl 53]: 343 – 349Google Scholar
  87. Vassar R, Bennett BD, Babu Khan S, Kahn S, Mendiaz EA, Denis P, Teplow DB, Ross S, et al (1999) Beta-secretase cleavage of Alzheimer’s amyloid precursor protein by the transmembrane aspartic protease BACE. Science 28886: 735 – 741CrossRefGoogle Scholar
  88. Wagner SL, Munoz B (1999) Modulation of amyloid beta protein precursor processing as a means of retarding progression of Alzheimer’s disease. J Clin Invest 104: 1329 – 1332PubMedCrossRefGoogle Scholar
  89. Weinstock M (1995) The pharmacotherapy of Alzheimer’s disease based on the cholinergic hypothesis: an update. Neurodegeneration 4: 349 – 356PubMedCrossRefGoogle Scholar
  90. Windisch M, Paier B, Eggenreich U (1994) Neuronal growth factors and their role in degenerative brain diseases: A mini-review. Neurologia Croatica 43 /2: 9 – 20Google Scholar
  91. Windisch M, Gschanes A, Hutter-Paier B (1998) Neurotrophic activities and therapeutic experience with a brain derived peptide preparation. J Neural Transm [Suppl 53]: 289 – 298Google Scholar
  92. Windisch M, Gschanes A, Hutter-Paier B (1999) The usefulness of neurotrophic factors for tretament of Alzheimer’s disease. Ann Psychiatry 7: 171 – 186Google Scholar
  93. Yaffe K, Sawaya G, Lieberburg I, Grady D (1998) Estrogen therapy in postmenopausalGoogle Scholar
  94. women: Effects on cognitive function and dementia. JAMA 279: 688–695Google Scholar
  95. Yamada K, Nitta A, Hasegawa T, Fuji K, Hiramatsu M, Kameyama T, Furukawa Y, Hayashi K, Nabeshimia T (1997) Orally active NGF synthesis stimulators: potential therapeutic agents in Alzheimer’s disease. Behav Brain Res 83: 117 – 122PubMedCrossRefGoogle Scholar

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Authors and Affiliations

  • M. Windisch
    • 1
  1. 1.JSW-Research Forschungslabor GmbHGrazAustria

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